Peer review of the pesticide risk assessment of the active substance 1-methylcyclopropene.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State The Netherlands for the pesticide active substance 1-methylcyclopropene are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council for an amendment in approval conditions. The current approval of 1-methylcyclopropene includes the specific provision 'Only uses as plant growth regulator for post-harvest storage in sealable warehouse may be authorised'. The applicant AgroFresh Holding France SAS submitted, in accordance with Article 7 of Reg. (EC) 1107/2009, an application to remove this specific provision in order to allow member states to authorise the use of products containing 1-methylcyclopropene on outdoor crops pre-harvest. The conclusions were reached on the basis of the evaluation of the representative use(s) of 1-methylcyclopropene as a plant growth regulator via spray application on pome fruit. The reliable endpoints, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance Phthorimaea operculella granulovirus.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, The Netherlands for the pesticide active substance Phthorimaea operculella granulovirus are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses of Phthorimaea operculella granulovirus as an insecticide on tomato (field and greenhouse uses) and on potato (field use) via spraying (tractor drawn or knapsack sprayers) or overhead irrigation. The reliable endpoints, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed.

B cell depletion for autoimmune liver diseases: A retrospective review of indications and outcomes.

Objectives: Pediatric autoimmune hepatitis has an incidence of 0.23/100.000 children in North America, with a bleak prognosis if left untreated. Steroids are the therapy of choice but are not always effective. B cell depletion is a safe and effective therapy that allows for a steroid-sparing protocol, especially in patients who do not tolerate side effects. Methods: We retrospectively reviewed rituximab-treated patients between 2017 and 2022. Demographics, previous treatments, reasons for B cell depletion, response, and adverse effects were noted. Results: Six patients with a mean age of 10.2 years were included. All patients had comorbidities that rendered treatment with steroids unsuccessful or undesirable. Rituximab was started at a mean follow-up of 8 months. After 6 months, the mean alanine transaminase and aspartate transaminase levels decreased from 575 IU/L and 342 IU/L, respectively, to 28 IU/L (p = 0.02) and 36 IU/L (p = 0.008), respectively. Mean γ-glutamyl transpeptidase decreased from 105 to 25 IU/L (p = 0.01). Immunoglobulin G levels were normalized in all patients (p = 0.01). No severe adverse events were observed. One patient had persistent hypogammaglobulinemia, and another had lymphopenia. Conclusion: B-cell depletion is an effective and safe treatment for autoimmune liver diseases and should be included as an option, particularly for relapsing patients in whom steroids are undesirable or have shown nonadherence.

Peer review of the pesticide risk assessment of the active substance Pythium oligandrum strain B301.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State Belgium for the pesticide active substance Pythium oligandrum strain B301 and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses of Pythium oligandrum strain B301 as a resistance inducer/elicitor to control trunk diseases on grapevines. The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Assessment of the 2022 post-market environmental monitoring report on the cultivation of genetically modified maize MON 810 in the EU.

Following a request from the European Commission, the European Food Safety Authority (EFSA) assessed the 2022 post-market environmental monitoring (PMEM) report on the cultivation of Cry1Ab-expressing maize event MON 810. Overall, the 2022 PMEM report provides no evidence of adverse effects of maize MON 810 cultivation. It shows a high level of compliance with refuge requirements by Spanish and Portuguese farmers growing maize MON 810, but uncertainty remains on compliance in areas where the clustered surface of maize MON 810 farms exceeds 5 ha. There are no signs of practical resistance to Cry1Ab in the field in corn borer populations collected in north-eastern Spain in 2022, although a decrease in Cry1Ab susceptibility in Mediterranean corn borer populations from this area cannot be excluded. Information retrieved through farmer questionnaires in Spain and from the scientific literature reveals no unanticipated adverse effects on human and animal health or the environment arising from the cultivation of maize MON 810. Uncertainties remain on whether 'very highly' and 'extremely' sensitive non-target lepidoptera are potentially exposed to harmful amounts of MON 810 pollen. EFSA notes that several recommendations made in the frame of the assessment of previous PMEM reports remain unaddressed and identified additional shortcomings in the 2022 PMEM report that require further consideration by the consent holder in future annual PMEM reports. Particularly, EFSA emphasises the urgent need to increase the sensitivity of the insect resistance monitoring strategy and implement mitigation measures to ensure that the exposure of non-target lepidoptera to maize MON 810 pollen is reduced to levels of no concern.

Peer review of the pesticide risk assessment of the active substance triclopyr (variant triclopyr-butotyl).

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Poland and co-rapporteur Member State Hungary for the pesticide active substance triclopyr (variant triclopyr-butotyl) and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of triclopyr (variant triclopyr-butotyl) as a herbicide on established pasture and non-recreational amenity grassland (field use). MRLs were assessed in rice. The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Genetic cholestasis: classification according to the cellular defect. / Colestasis genéticas: clasificación según el defecto celular.

Advances in molecular biology achieved during the last years have allowed us to know the genes involved in biliary secretion and the mutations capable of generating cholestasis. The mechanisms involved in forming bile and its circulation have been clarified. According to the biology of biliary secretion, we classify the genetic causes of cholestasis as follows: 1) transport abnormalities in canalicular or basolateral membranes, 2) alterations in intracellular vesicle transit, 3) increased paracellular permeability, 4) mutations in nuclear receptors, 5) cholangiopathies, and 6) hepatocellular diseases, due to disturbance of the function of intracellular organelles or errors of metabolism. This physiopathological classification of chronic cholestasis in childhood will facilitate pediatricians' diagnostic guidance and timely specialized referrals, as patients should receive early and appropriate treatment for its complications.

Los avances en biología molecular alcanzados durante los últimos años nos han permitido conocer los genes que intervienen en la secreción biliar y las mutaciones capaces de generar un cuadro de colestasis. Los mecanismos involucrados en la formación de la bilis y su circulación han sido precisados. De acuerdo a la biología de la secreción biliar, clasificamos las causas genéticas de colestasis en 1) anomalías del transporte en las membranas canalicular o basolateral, 2) alteraciones del tránsito de vesículas intracelulares, 3) aumento de la permeabilidad paracelular, 4) mutaciones en los receptores nucleares, 5) colangiopatías, 6) enfermedades hepatocelulares, por perturbación de la función de orgánulos intracelulares o errores del metabolismo. Esta clasificación fisiopatológica de las colestasis crónicas de la infancia facilitará la orientación diagnóstica de los pediatras y la derivación especializada oportuna, ya que los pacientes deben recibir tempranamente un tratamiento adecuado a las complicaciones de la colestasis.

Peer review of the pesticide risk assessment of the active substance mepiquat (evaluated variant mepiquat chloride).

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Finland, and co-rapporteur Member State, Estonia, for the pesticide active substance mepiquat (evaluated variant mepiquat chloride) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of mepiquat chloride as a plant growth regulator on cereals and grass (field uses). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Lack of differences in outcomes between 3 immunosuppression protocols in the first year after pediatric liver transplantation: A multicenter study.

Advances in immunosuppression have extended patient and graft survival rates after solid organ transplantation; however, this is not free of side effects. Balancing safety and efficacy is of paramount importance, particularly in the pediatric setting. Current literature comparing different protocols is scarce, and decisions are mostly guided by physician preference. We aimed to compare 3 different protocols from 4 different centers to identify differences in outcomes after 1 year of follow-up. A retrospective analysis of the databases of the participating centers was performed. Consecutive patients aged <18 years with a first liver-only transplant and no other underlying congenital or acquired immunodeficiency were included. Patients were classified according to the immunosuppression protocol as follows: group A (prednisone + tacrolimus + basiliximab), group B (prednisone + tacrolimus + basiliximab + antithymocyte globulin), and group C (prednisone + tacrolimus). Differences in survival, frequency of rejection, infections, and other complications were analyzed in the entire group (n = 97) and the group with biliary atresia (n = 48). After 1 year of follow-up, no differences in patient or graft survival were observed when comparing either the entire group (n = 97) or patients with biliary atresia only (n = 48). The frequencies of rejection and episodes of infection were similar. Renal function showed no differences either before or after transplantation or between the groups. Immunosuppression protocols used in this study appeared to be equally safe and effective. This could offer the opportunity to tailor them to the patient's individual characteristics without compromising the outcome.

Peer review of the pesticide risk assessment for the active substance difenoconazole in light of confirmatory data submitted.

The conclusions of the EFSA following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State, Spain, for the pesticide active substance difenoconazole are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory information with regard to the consumer risk assessment. The conclusions were reached on the basis of the evaluation of the representative uses of difenoconazole as a fungicide on pome fruit, carrot, wheat, barley, triticale, rye and oats. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and/or literature in the dossier peer reviewed, are presented. Concerns were not identified.

Peer review of the pesticide risk assessment of the active substance paraffin oil (CAS 8042-47-5, chain lengths C17-C31).

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Greece, and co-rapporteur Member State, France, for the pesticide active substance paraffin oil are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of paraffin oil as an acaricide and insecticide on potatoes, ornamentals (flower bulbs) and orchards (pear/apple), on pome fruit and stone fruit, on field and permanent protected fruiting vegetables and on field and permanent protected roses and on citrus. The reliable end points appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Illuminating Pathways to Dynamic Nanotribology: Light-Mediated Active Control of Interfacial Friction with Nanosuspensions.

Active control of nanotribological properties is a challenge. Materials responsive to external stimuli may catalyze this paradigm shift. Recently, the nanofriction of a thin film is modulated by light, ushering in phototribology. This frontier is expanded here, by investigating photoactive nanoparticles in lubricants to confer similar functionality to passive surfaces. Quartz-crystal microbalance (QCM) is employed to assess the phototribological behavior of aqueous suspensions of titanium dioxide nanoparticles. A comparison of dark and illuminated conditions provides the first demonstration of tuning the interfacial friction in solid-nanosuspension interfaces by light. Cyclic tests reveal reversible transitions between higher (dark) and lower friction (illuminated) regimes. These transitions are underpinned by transient states with surface charge variations, as confirmed by Zeta potential measurements. The accumulated surface charge increases repulsion within the system and favors sliding. Upon cessation of illumination, the system returns to its prior equilibrium state. These findings impact not only nanotribology but nanofluidics and nanorheology. Furthermore, the results underscore the need to consider light-induced effects in other scenarios, including the calculation of activity coefficients of photoactive suspensions. This multifaceted study introduces a new dimension to in operando frictional tuning, beckoning a myriad of applications and fundamental insights at the nanoscale.

Hyperosmolarity in children with hyperammonemia: a risk of brain herniation at the start of renal replacement therapy.

Purpose: Renal replacement therapy (RRT) is used in hyperammonemia to reduce the concentration of ammonia in the blood. In the case of plasma hyperosmolarity, RRT can also rapidly decrease plasma osmolarity, which may increase cerebral edema in these patients and favor the occurrence of brain herniation. Methods: We conducted a retrospective clinical study in a tertiary care university-affiliated hospital. All patients admitted in a Pediatric Intensive Care Unit (PICU), less than 18 years old with ammonemia >150 µmol/L and who underwent RRT between January 2015 and June 2023 were included. We collected data on plasma osmolarity levels, osmolar gap and blood ammonia levels before and during RRT. Results: Eleven patients were included (10 with acute liver failure and 1 with a urea cycle disorders). Their mean age was 36.2 months. Before RRT, the median highest measured osmolarity was 320 (305-324) mOsm/L, whereas the median calculated osmolarity was 303 (293-314) mOsm/L, corresponding to an osmolar gap of 14 mOsm/L. Ammonia blood level over 400 µmol/L are significantly associated with higher plasma osmolarity (P-Value <0.001). In one case, a patient had a brain herniation episode after a quick osmolar drop. This episode was reversed by the administration of hyperosmolar agents and the temporary suspension of RRT. Conclusion: This study highlights the hyperosmolarity and high osmolar gap that occur in children with hyperammonemia. A careful monitoring and control of plasma osmolarity evolution may alert clinician on the risk of occurrence of neurological complication such as brain herniation.

Implication of the Annexin 1/FPR axis in leishmanial exosome-mediated Leishmania major skin hyperpathogenesis.

Introduction: Exosomes produced by the protozoan parasite Leishmania (LeishEXO) are well-established drivers of virulence, though mechanisms underlying their exacerbation of experimental leishmaniasis remain elusive. Expression of Annexin A1 (ANXA1), a protein implicated in exosome-mediated pathologies and viral internalization, has been shown to correlate with cutaneous leishmaniasis severity. Given ANXA1's regulation of myeloid cells - the canonical hosts for Leishmania - we studied the potential role of ANXA1 and its receptors FPR1/2 in exerting LeishEXO's effects. Methods: Murine and in vitro ANXA1-/- models were used to study the generation of protective TH1 responses during experimental L. major infection with and without LeishEXO. Recruitment of inflammatory cells was assessed using a peritoneal cell recruitment assay and immunophenotyping, and production of inflammatory mediators was measured using a cytokine and chemokine array. Treatment of experimental models with FPR2 antagonist WRW4 and FPR1/2 agonist WKYMVm was used to delineate the role of the FPR/ANXA1 axis in LeishEXO-mediated hyperpathogenesis. Results: We established that ANXA1 deficiency prohibits LeishEXO-mediated pathogenesis and myeloid cell infection, with minimal alterations to adaptive and innate immune phenotypes. FPR2 blockade with WRW4 similarly inhibited leishmanial hyperpathogenesis, while direct activation of FPRs with WKYMVm enhanced infection and recapitulated the LeishEXO-mediated phenotype. This research describes LeishEXO's utilization of the ANXA1/FPR axis to facilitate parasitic internalization and pathogenesis, which may be leveraged in the development of therapeutics for leishmaniasis.

Peer review of the pesticide risk assessment of the active substance lenacil.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Belgium, and co-rapporteur Member State, Austria, for the pesticide active substance lenacil are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of lenacil as a herbicide on sugar and fodder beet (field use). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Novel Reference Method for the Characterization of PD Measuring Systems Using HFCT Sensors.

During their lifespan, high-voltage (HV) electrical systems are subjected to operating conditions in which electrical, mechanical, thermal and environmental-related stresses occur. These conditions over time lead to unforeseen failures caused by various types of defects. For this reason, there are several technologies for measuring and monitoring the electrical systems, with the aim of minimizing the number of faults. The early detection of defects, preferably in their incipient state, will enable the necessary corrective actions to be taken in order to avoid unforeseen failures. These failures generally lead to human risks and material damage, lack of power supply and significant economic losses. An efficient maintenance technique for the early detection of defects consists of the supervision of the dielectrics status in the installations by means of on-line partial discharge (PD) measurement. Nowadays, there are numerous systems in the market for the measurement of PD in HV installations. The most efficient with a reasonable cost will be those that offer greater security guarantees and the best positioned in the market. Currently, technology developers and users of PD measuring systems face difficulties related to the lack of reference procedures for their complete characterization and to the technical and economic drawback of performing the characterization tests on site or in laboratory installations. To deal with the previous difficulties, in this paper a novel method for the complete and standardized characterization of PD measuring systems is presented. The applicability of this method is mainly adapted for the characterization of systems operating in on-line applications using high-frequency current transformer (HFCT) sensors. For the appropriate application of the method, an associated and necessary scale modular test platform is used. In the test platform, the real on-site measuring conditions of an HV insulated distribution line are simulated in a controlled way. Practical characterizations, showing the convenience and advantages of applying the method using the modular test platform, are also presented.

Pancreas units within gastroenterology departments. Organizational and operational standards for a patient-centered service. / Las unidades de páncreas en los servicios de aparato digestivo. Estándares de organización y funcionamiento para un servicio centrado en el paciente.

The Asociación Española de Pancreatología (AESPANC), Asociación Española de Gastroenterología (AEG), and Sociedad Española de Patología Digestiva (SEPD) have developed a consensus document on the standards and recommendations they consider essential for the organization of pancreas units (PUs) within gastroenterology services (GSs) in order to conduct their activities in an efficient, high-quality manner. The consensus document defines PUs and lays down standards relating to their organization, structure, service portfolio, processes, and teaching and research activities. Standards have been categorized as mandatory (requirements to be met to qualify for certification by the scientific societies responsible for the standards) or recommendations. Standards should be updated at most within five years based on the experience gained in Spanish PUs and the advance of knowledge regarding pancreas disease. Development of health outcome indicators, including patient-reported outcome measures (PROMs), is considered a relevant challenge, as is evidence on the association of PU structure and activity standards with health outcomes.

Pancreas units within gastroenterology departments. Organizational and operational standards for a patient-centered service.

The Asociación Española de Pancreatología (AESPANC), Asociación Española de Gastroenterología (AEG), and Sociedad Española de Patología Digestiva (SEPD) have developed a consensus document on the standards and recommendations they consider essential for the organization of pancreas units (PUs) within gastroenterology services (GSs) in order to conduct their activities in an efficient, high-quality manner. The consensus document defines PUs and lays down standards relating to their organization, structure, service portfolio, processes, and teaching and research activities. Standards have been categorized as mandatory (requirements to be met to qualify for certification by the scientific societies responsible for the standards) or recommendations. Standards should be updated at most within five years based on the experience gained in Spanish PUs and the advance of knowledge regarding pancreas disease. Development of health outcome indicators, including patient-reported outcome measures (PROMs), is considered a relevant challenge, as is evidence on the association of PU structure and activity standards with health outcomes.

Treatment of the neck in residual/recurrent disease after chemoradiotherapy for advanced primary laryngeal cancer.

Concomitant chemoradiotherapy (CRT) is extensively used as primary organ preservation treatment for selected advanced laryngeal squamous cell carcinomas (LSCC). The oncologic outcomes of such regimens are comparable to those of total laryngectomy followed by adjuvant radiotherapy. However, the management of loco-regional recurrences after CRT remains a challenge, with salvage total laryngectomy being the only curative option. Furthermore, the decision whether to perform an elective neck dissection (END) in patients with rN0 necks, and the extent of the neck dissection in patients with rN + necks is still, a matter of debate. For rN0 patients, meta-analyses have reported occult metastasis rates ranging from 0 to 31 %, but no survival advantage for END. In addition, meta-analyses also showed a higher incidence of complications in patients who received an END. Therefore, END is not routinely recommended in addition to salvage laryngectomy. Although some evidence suggests a potential role of END for supraglottic and locally advanced cases, the decision to perform END should weigh benefits against potential complications. In rN + patients, several studies suggested that selective neck dissection (SND) is oncologically safe for patients with specific conditions: when lymph node metastases are not fixed and are absent at level IV or V. Super-selective neck dissection (SSND) may be an option when nodes are confined to one level. In conclusion, current evidence suggests that in rN0 necks routine END is not necessary and that in rN + necks with limited nodal recurrences SND or a SSND could be sufficient.

Peer review of the pesticide risk assessment of the active substance clove oil.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, Malta, for the pesticide active substance clove oil are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions for the amendment of approval were reached on the basis of the evaluation of the representative use of clove oil as a preharvest nematicide on tomatoes and cucumbers (permanent greenhouse use). The representative use evaluated for the renewal of approval of clove oil was as post-harvest fungicide and bactericide on apples, pears and peaches (indoor uses). The reliable endpoints appropriate for use in regulatory risk assessment are presented. Endpoints not relevant to the scope of the proposed amendment of approval conditions will be addressed in the context of the renewal of approval procedure of clove oil running in parallel (AIR IV, EFSA Q-2016-00809). Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.